Results The SHAPS non-psychopaths and those with schizoid
personality disorders had enhanced 5-HT function (prolactin response to
d-fenfluramine). Reduced 5-HT function was found in offenders with
DSM-III-R borderline personality disorders and those with a history of
repeated self-harm or alcohol misuse. The 5-HT function was inversely
correlated more strongly with impulsivity than with aggression. Plasma
testosterone correlated positively with aggressive acts. The SHAPS primary
psychopaths had lower initial cortisol and higher testosterone concentrations
than controls.

A main focus of studies examining the biological determinants of aggressive
behaviour has been the association between low serotonergic (5-HT) function
and impulsive aggression in studies of the cerebrospinal fluid (CSF)
concentration of the 5-HT metabolite 5-hydroxyndoleacetic acid (5-HIAA;
Tuinier et al, 1995)
and from 5-HT drug challenge studies
(Markowitz & Coccaro,
1995). In contrast, testosterone has been implicated primarily in
aggressive rather than impulsive behaviour
(Archer, 1991). The notion that
a low 5-HT level relates more to impulsivity and that testosterone relates
more to aggression receives support from CSF studies
(Virkkunen et al,
1994). We investigated relationships between impulsivity,
aggression, 5-HT function and testosterone in controls and in offenders with
personality disorders, minimising potential confounding factors due to organic
brain conditions and drug and alcohol misuse, and tested the hypothesis that
reduced 5-HT function would be seen only in the subgroup of aggressive
offenders with high impulsivity and not in those with normal or low
impulsivity.

All subjects were interviewed and screened for DSM-III-R Axis I and II
disorders using the Structured Clinical Interview Diagnosis (SCID-I and II)
schedules (Spitzer et al,
1990). Exclusion criteria for all subjects included age >55
years, alcohol intake >50 units per week in the past year, illicit drug or
steroid use in the last 5 years, psychotropic medication in the last 6 weeks,
a history of head trauma and abnormal blood biochemistry. Additional exclusion
criteria for controls were an Axis II diagnosis (SCID-II;
Spitzer et al,
1990).

Diagnostic/group assignment

The SHAPS was used as the primary instrument for group assignment among
patients because DSM-III-R Axis II diagnoses were not mutually exclusive in
this group. It has been validated in forensic samples
(Blackburn, 1986) and provides
distinct personality groupings, based on the orthogonal dimensions of
belligerence (related to impulsivity and hostility) and withdrawal (relating
to anxiety and introversion), within which several Axis II personality
disorders will fall. Fifty-one patients were classified as SHAPS psychopaths
(high belligerence scores) and nine as SHAPS non-psychopaths (low belligerence
scores). The majority of the controls were classified as SHAPS
non-psychopaths, but five had sub-scale scores that reflected some ‘
psychopathic’ traits. The latter were not excluded because they
did not meet DSM criteria for a diagnosis of Axis II personality disorders. Of
the SHAPS psychopaths, 21 were primary (low withdrawal scores) and 30 were
secondary psychopaths (high withdrawal scores).

The majority (42) of SHAPS psychopaths had Cluster B DSM-III-R diagnosis.
Several SHAPS psychopaths, however, also met the criteria for one or more
Cluster A/C diagnoses, including that for avoidant (3), dependent (6),
paranoid (5) and passive aggressive (13) personality. Among the SHAPS
non-psychopathic group, six met the criteria for obsessional, two for
narcissistic and seven for schizoid personality disorders.

Serotonin drug challenge and biochemical measures

The responsivity of the 5-HT system was assessed using the prolactin (PRL)
response to an oral 30-mg d-fenfluramine (dFEN) challenge,
which is believed to act primarily at 5-HT2 receptor sites
(DiRenzo et al, 1989)
and is more 5-HT-specific than d,l-fenfluramine
(Garattini et al,
1979). Sixty patients and 27 control subjects received
dFEN, with 40 patients and 21 controls receiving a placebo (PBO)
challenge in a single-blind fashion separated by at least 1 week. No
significant order effects were observed in the baseline PRL levels or PRL
responses to challenge with PBO or dFEN. Subjects attended the
research room at about 10.30 a.m. after a light breakfast. An intravenous
catheter was inserted in a forearm vein at 11.00 a.m. and kept open with a
heparin lock. Blood samples were taken immediately after cannulation, then 60
minutes later immediately before oral administration of identical capsules
that contained either dFEN or PBO (time zero), and at hourly
intervals for a further 5 hours (+300 min).

Plasma PRL and cortisol (CORT) levels were obtained at all time points,
testosterone on time zero samples and dFEN/norfenfluramine on samples
from +60 or +300 min. Subjects remained awake and fasting and completed the
Profile of Mood States (POMS; McNair
et al, 1981) hourly.

Biochemical assay methods

Blood samples were placed on ice, with plasma separated at 2000 rpm and
stored at -20°C until assay. The lower limit of detection for PRL
(IRMA-NETRIA, London) was 24mIU/l, with intra- and inter-assay variability
less than 2.4% and 4.8%, respectively. The respective values for CORT
([125I]radioimmunoassay, Bioclin, Cardiff) were 0.2μg/dl, 4.3%
and 5.8%. For dFEN and norfenfluramine concentrations (gas-liquid
chromatography) lower limits of detection were 0.5 and 2ng/ml, with intra- and
inter-assay coefficients of variation of 6.9% and 2.7%, respectively. For
testosterone (solidphase radioimmunoassay, DPC, Los Angeles, CA) the values
were 0.04 ng/ml, 5.2% and 5.9%. The normal range was 2.8-6.0 ng/ml.

Data analysis

Impulsivity and aggression were difficult to separate, so in addition to
analysing the rating scales separately, composite scores likely to weight
towards either impulsivity or aggression were derived for each dimension.
Impulsivity scores from the SHAPS, BIS and IVE were converted into
z-scores and summed to form a composite impulsivity measure.
Similarly, a composite aggression score was calculated from a summation of the
z-scores on the BDHI motor aggression factor (assault, indirect
aggression, verbal aggression and irritability), BGA total score and SHAPS
aggression scale.

Testosterone values from the two occasions were averaged. As plasma
dFEN and norfenfluramine were analysed separately and as a combined
drug measure did not differ, only the combined drug measure is reported. The
area under the curve (AUC) was calculated for hormonal and drug measures by
the trapezoid method, corrected for baseline differences taken as +60 minutes
after drug administration because this offered the most stable baseline with
undetectable drug levels until after this point. Placebo-corrected hormonal
AUC values were obtained by subtracting those after PBO from those after
dFEN.

Statistical analysis

Data were analysed using SPSS for Windows Release 6 (SPSS Inc., Chicago,
IL). Analysis of variance (ANOVA) was used with one between-group factor
(controls, SHAPS psychopaths, SHAPS non-psychopaths) and one within-group
factor (drug). As fewer subjects had both a placebo and dFEN
challenge rather than a dFEN challenge alone, and there were few
differences between the findings, we report the dFEN challenge data
only unless a different result was obtained using placebo data, in which case
both are presented. Least significant differences (LSD) were used for post
hoc comparison. Where post hoc tests revealed significant group
differences, t-tests were used to assess the magnitude of these
significant differences. Drug levels were used as covariates. Correlations
between variables were determined by Spearman's correlation coefficients.
Unless stated otherwise, correlations relate to the total sample. Stepwise
regression analyses were used to explain the relative contributions of
variables that contributed to the variance in PRL response to fenfluramine,
that is, the 5-HT function.

RESULTS

Psychometric characteristics of the sample

The SHAPS non-psychopaths and psychopaths had higher composite aggression
scores than controls (F(2,84)=69.3, P<0.001) (see
Table 1). The significantly
higher aggression score among SHAPS psychopaths compared with controls and
SHAPS non-psychopaths was due to to higher scores on the BDHI motor aggression
subscale (F(2,84)=33.71, P<0.001) and BDHI attitudinal
hostility scales (F(2,84)=38.59, P<0.001). On the BGA,
SHAPS psychopaths and non-psychopaths had higher scores than controls
(F(2,84)=105.37, P<0.001), but SHAPS psychopaths and
non-psychopaths did not differ significantly on this measure. Significant
differences between non-psychopaths and controls were attributable to higher
scores in non-psychopaths on the BDHI assault item and the BGA. Primary and
secondary psychopaths did not differ significantly in aggression ratings.

Impulsivity scores

The SHAPS psychopaths had significantly higher composite impulsivity scores
than controls and non-psychopaths (F(2,84)=59.50,
P<0.001). This pattern of group differences applied to all
sub-scales of the composite score. The SHAPS nonpsychopaths tended to have
lower scores than controls on all impulsivity measures but the differences did
not reach significance. Although secondary psychopathic patients had higher
impulsivity scores than primary psychopaths, these differences did not reach
significance.

Mood measures

There were no significant group differences in BDI score
(F(2,84)=1.91, P=0.15). The SHAPS psychopaths, however,
demonstrated significantly higher scores on the STAI (F(2,84)=5.05,
P<0.01), which was attributable solely to the secondary psychopath
group.

Biochemical/hormonal data

Despite differences in anxiety score, primary and secondary psychopaths did
not differ on biochemical measures, so for ease of interpretation the
psychopaths are presented as a single group. Mean hormonal concentrations and
responses to challenge are shown in Table
2.

Prechallenge and baseline biochemical (hormonal) measures

There was a trend towards significant group differences
(F(2,81)=2.49, P=0.08) in plasma testosterone, with SHAPS
psychopaths showing higher mean levels than controls. These differences were
due primarily to primary psychopaths (mean=6.24, s.d.=1.41) having higher
testosterone levels than controls (mean=5.03, s.d.=1.48; t=-2.80,
d.f.=44, P<0.01).

Plasma CORT concentrations at the time of cannulation were significantly
higher in controls compared with psychopaths but not non-psychopaths
(F(2,84)=4.41, P<0.01). However, this difference
disappeared by baseline (+60 min) due to a significantly greater drop in CORT
concentration between cannulation and baseline in controls compared with
psychopaths (F(2,84)=7.84, P<0.001). Non-psychopaths
showed an intermediate drop (Table
2).

There were no significant group differences in PRL concentration at
cannulation (F(2,84)=0.06, P=0.98) or baseline
(F(2,84)=0.99, P=0.37).

Drug challenge data

The challenge tests were well tolerated and the only observed group
difference was on the POMS fatigue measure, where SHAPS psychopaths reported
more fatigue than controls based on an analysis of the AUC data (mean=14.6,
s.d.=19.0 v. mean=4.2, s.d.=10.1; F(2,80)=3.57,
P<0.05).

Fenfluramine drug levels

There were no differences between controls and SHAPS-defined
(F(2,84)=1.24, P=029) or DSM-III-R-defined groups
(F(2,84)=1.10, P=0.33) on the drug metabolism AUC data.

Biochemical measures in controls and SHAPS category patients

Administration of dFEN resulted in significant PRL responses in an
analysis of the PBO-corrected data (F(2,58)=6.08,
P<0.01). By using the dFEN challenge occasion alone there
was a significant effect of group (F(2,84)=6.17, P<0.01),
with non-psychopathic patients having higher responses than either controls or
psychopaths (Fig. 1 and
Table 2). Differences between
controls and psychopaths showed a trend towards significance (t=1.68,
d.f.=76, P=0.09).

In a comparison of PRL AUCs in patients with a specific diagnosis of
personality disorder, controls and the remaining patients with personality
disorder who did not meet the criteria for that diagnosis, significant group
differences were observed only for those with diagnoses of borderline
(F(2,84)=3.58, P<0.05), schizoid (F(2,84)=8.62,
P<0.001) and obsessional personality disorder
(F(2,84)=5.51, P<0.01). A trend towards a significant
group difference was observed for a diagnosis of antisocial personality
disorder (F(2,84)=2.65, P=0.07). Stepwise multiple
regression analysis confirmed that only those with borderline (low PRL
response) and schizoid (high PRL response) personalities contributed
significantly to the variance in PRL AUC response to dFEN
(r2=0.15; F(2,84)=7.74, P<0.01).

Prolactin response in controls and patients who self-harm

A comparison of controls (no self-harm), patients with no history of
self-harm (n=22), patients with one or two attempts (n=16)
and patients with multiple (more than three) attempts (n=22) revealed
a trend towards lower PRL responses in high-frequency self-harmers compared
with controls (F(3,83)=1.88, P=0.13), which was significant
when the PBO-corrected AUC data were used (F(3,57)=3.21,
P<0.05) (see Table
3).

Prolactin response in controls and patients with/without an
illicit-drug history

Of the 23 patients with a previous history of drug misuse (minimum
abstinence of 5 years), the majority had used cannabis and only four were
cocaine users. There were no significant differences in dFEN
metabolism or PRL response to dFEN in controls (non-drug-users) and
patients with and without drug use (F(2,84)=1.26, P=0.28)
(see Table 3). Covarying for
fenfluramine level did not alter the findings.

Prolactin response in controls and patients with/without an alcohol
history

Of the 28 patients with a prior history of alcohol misuse, the mean
abstinence period was 5 years (range 1.6-15 years). Drug metabolism
(dFEN) did not differ in patients with and without a history of
alcohol misuse. Differences in PRL response to dFEN were observed
between controls and patients with and without a history of alcohol misuse
(F(2,84)=4.36, P<0.01). Mean PRL responses were lower in
patients with a history of alcohol misuse than in patients without a history
of alcohol misuse (t=2.8, d.f.=58, P<0.01) and controls
(t=2.22, d.f.=53, P<0.05) (see
Table 3). Differences in PRL
responses between controls and SHAPS psychopaths and non-psychopaths still
showed a trend towards significance (F(2,36)=2.79, P=0.06)
when patients with a history of alcohol misuse were excluded. These
differences reached significance when dFEN drug levels were used as
covariates (F(3,55)=3.59, P<0.05).

Biochemical measures: intercorrelations

Baseline (+60 min) CORT and PRL levels did not correlate significantly
(r=0.16, P=0.12), whereas the PRL and CORT responses to
dFEN did correlate significantly (r=0.45,
P<0.001). Testosterone levels did not correlate with either
measure. Baseline CORT correlated negatively with the CORT response to
dFEN (r=-0.45, P<0.001) and baseline PRL with
PRL response to dFEN (r=-0.20, P=0.06).

Impulsivity/aggression and 5-HT

Correlations between hormonal data and psychometric measures are shown in
Table 4. There were significant
negative correlations between PRL response and composite impulsivity and
aggression scores, which were largely attributable to significant individual
associations between PRL response and IVE impulsivity, BIS scores (see
Table 4) and BDHI indirect
aggression scores (r=-0.25, P<0.05). A trend towards a
significant inverse relationship with BDHI irritability (r=-0.20,
P=0.06) was also noted. Analysis of the correlations in the larger
patient sample alone gave the same results. Although BDI score correlated with
impulsivity, there was no significant correlation between depression score and
PRL response.

The CORT AUC did not correlate significantly with any of the psychometric
measures, whereas testosterone showed a positive correlation with BGA and the
non-planning sub-scale on the BIS, which reflects a failure to plan ahead.

Impulsivity, aggression, alcohol misuse and 5-HT

To clarify further the relative contribution of impulsivity, aggression and
alcohol misuse to PRL response, these variables were entered into a stepwise
multiple regression analysis with PRL response as the dependent variable.
Impulsivity was entered in step 1 (multiple R=0.28,
F(1,85)=7.78, P=0.006) and alcohol misuse in step 2
(multiple R=0.33, F(2,84)=6.21, P=0.003).
Aggression score was not accepted in the equation. Standardised beta (β)
weights for impulsivity (β=0.39, P=0.0008) were higher than for
alcohol misuse (β=0.23, P=0.04), indicating that impulsivity
makes a greater contribution than a history of alcohol misuse to PRL
response.

DISCUSSION

The main finding from this study is a dimensional relationship between 5-HT
function and impulsivity. At the impulsive end of the spectrum, lower PRL
responses to dFEN tended to occur in those defined as SHAPS
psychopaths and those with DSM-III-R Axis II Cluster B disorders, particularly
borderline personality disorders. At the low impulsive, or ‘
inhibited’ end of the spectrum, the aggressive offenders
categorised as SHAPS non-psychopaths and those with DSM-III-R Cluster A/C
diagnosis (e.g. schizoid/obsessional personality disorders) had increased PRL
responses to dFEN compared with controls. Measures of aggression also
showed a significant negative correlation with 5-HT function but the relative
importance of impulsivity as opposed to aggression in relationship to 5-HT
function is extremely difficult to tease out, given the high correlation
between impulsivity and aggression measures. The regression analysis, however,
suggests that impulsivity makes a greater contribution to 5-HT function than
composite aggression scores. Impulsivity as a dimension of extraversion (IVE)
showed the strongest correlation with 5-HT function. Other findings of
interest were the positive correlation between plasma testosterone and
aggressive acts and the lower plasma cortisol concentration immediately after
cannulation in SHAPS psychopaths, which may be a reflection of lower arousal
in response to aversive stimulation in this group.

Methodological issues

Recruiting from maximum-security hospitals allowed us to investigate a
population with personality disorders who were ‘pharmacologically
clean’ in terms of recent illicit drug/alcohol misuse and prescribed
psychotropic medication, thus minimising these confounding factors. Sampling
patients and controls from the same institution also allowed some degree of
control for the effects of environment, but the findings may not be truly
representative of other samples of offenders with personality disorders or of
controls. The fact that five staff controls had high scores on measures
designed to tap anti-authoritarian attitudes and aggressive traits (SHAPS)
suggests that some ‘normal’ subjects may be more aggressive than
the general population. In terms of the overall findings of the study,
however, it is possible that a comparison with a community sample of controls
would have resulted in even greater observed differences between controls and
psychopathic patients on measures of 5-HT function. The psychometric measures
used in this study were selected so that comparisons could be drawn with
previous studies in the field. The SHAPS was chosen for patient group
assignment because it was validated in forensic populations and allowed
categorisation of subjects on the basis of impulsivity and aggression
(belligerence) dimensions, overcoming some of the problems of comorbid Axis II
pathology in patients.

Although the PRL response to challenge by the dFEN is a dynamic
index of 5-HT function, it reflects 5-HT synaptic activity in the hypothalamus
and may not give a picture of 5-HT function in other parts of the brain, such
as the frontal lobes, believed to be relevant to impulse control. At present,
there are no established techniques for assessing regional 5-HT function in
humans, although it is of interest that Siever et al
(1999) reported reduced
cerebral glucose utilisation using positron emission tomography in the frontal
lobes of six subjects with impulsive aggressive behaviour compared with
controls following dFEN administration, suggesting that 5-HT function
also may be reduced in this region.

Relationship between impulsivity and aggression

In this study, impulsivity and aggression measures tended to correlate
highly with each other. The SHAPS non-psychopathic offenders scored similar to
controls on the SHAPS aggression sub-scale but higher than controls on other
measures of aggression (BDHI assault and the BGA), consistent with their
offences. The SHAPS sub-scale of aggression measures irritable/angry
aggression rather than assault, which may account for these findings, but
alternatively it may be less likely to suffer from ceiling effects because it
was designed for use in forensic populations. The SHAPS non-psychopaths scored
near control values on impulsivity measures, with non-significantly lower
scores on the IVE than controls. This suggests that low impulsivity as part of
the dimension of extraversion (IVE) may be an important component in
determining group membership. The impulsivity measures may, however, have
demonstrated floor effects and not been able to detect ‘
overcontrol’ or ‘inhibition’ in this small group who
had strikingly large PRL responses.

Impulsivity tended to correlate with anxiety and depression scores. Similar
findings have been reported by others
(Apter et al, 1990),
who suggest that these variables represent a serotonergically linked cluster.
The association of anxiety measures with impulsivity and aggression argues
against a simple model of impulsive aggression being due to low fear, as has
been suggested for primary psychopaths
(Fowles, 1980), but does not
exclude subgroups of individuals for whom this might be true.

Serotonin function in relation to impulsivity and aggression

Our findings confirm previous reports
(O'Keane et al, 1992;
Coccaro et al, 1998)
that subjects characterised by high levels of impulsivity and aggression have
reduced central 5-HT function revealed using the 5-HT specific challenge agent
dFEN. That SHAPS psychopaths and those with borderline personality
disorders have blunted PRL responses to dFEN is in line with Coccaro
et al's (1989)
findings using d,l-fenfluramine and points to impulsivity as a
significant correlate of 5-HT function. The overlap between diagnoses of
personality disorders makes it unlikely that low 5-HT function is a
characteristic linked to specific personality disorders. In contrast to
previous research in this area, we identified a small subgroup of offenders
with elevated 5-HT function. It has been reported, however, that subjects with
obsessive-compulsive disorder (Insel
et al, 1985) and those with schizoid/autistic traits
(Sedvall et al, 1980;
McBride et al, 1989)
have elevated 5-HT function. This suggests that 5-HT may influence a
behavioural dimension with aspects of inhibition overcontrol at one end and
impulsivity at the other.

In this study, PRL response to dFEN did not correlate with anxiety
or depression in either controls or patients. Rydin et al
(1982) reported high anxiety
and hostility scores in subjects with low CSF 5-HIAA, which would concur with
our findings in SHAPS secondary psychopaths but subjects with impulsive
aggressive behaviour without elevated anxiety also showed evidence of reduced
5-HT function. The relationship between anxiety, impulsivity/aggression and
5-HT remains unclear and it is likely that it is much more complex than can be
illuminated using a single global measure of 5-HT function such as in this
study. For example, there is evidence for differing roles for 5-HT depending
on the type of anxiety and site of action in the brain
(Deakin & Graeff, 1991).
The PRL responses to dFEN are believed to be mediated through
5-HT2 receptors and it is known that other receptors such as the
5-HT1A receptor also play a role in anxiety
(Hollister, 1994) and
aggression (see Mak et al,
1995).

In line with previous reports, we found that alcohol misuse is related to a
low 5-HT state and this may be a significant confounding factor in studies of
5-HT and aggression (see Markowitz &
Coccaro, 1995, for a review). Our findings, however, suggest that
alcohol misuse does not satisfactorily account for the observed relationships
between impulsivity and 5-HT function.

As in Coccaro et al's
(1989) study, we were unable
to report an association between a history of drug misuse and 5-HT function.
Previous studies addressing comorbid impulsivity/aggression and drug misuse
(Fishbein et al,
1989; Moss et al,
1990) have produced conflicting findings. The discrepancies
observed may relate to the sample characteristics, but also to the types of
drugs used.

We observed a tendency to lower PRL responses in patients with a history of
repetitive self-harming behaviour. The frequency of self-harm correlated
positively with impulsivity and aggression measures and with anxiety and
depression scores. However, the lack of relationship between mood measures and
5-HT function suggests that the dimension of impulsivity/aggression is more
important in determining self-harming behaviour.

We did not find significant CORT responses to dFEN, which is
likely to explain the lack of relationship between CORT measures and
impulsivity. The PRL and CORT responses to 5-HT challenge are probably
mediated by different serotonergic receptors
(Coccaro, 1992) and there is
some evidence that CORT responses to FEN may be mediated by non-5-HT
mechanisms (Van de Klar & Bethea,
1982). We observed a significantly lower post-cannulation plasma
CORT concentration in SHAPS psychopaths, particularly primary psychopaths,
than controls, possibly suggesting a lower than normal physiological stress
response at the prospect of the invasive procedure. This finding concurs with
previous reports that ‘criminal psychopaths’, particularly ‘
primary psychopaths’, have reduced levels of stress prior to
anxiety-provoking situations and display electrodermal hyporesponsiveness when
anticipating aversive stimulation (Hare,
1978).

Testosterone and impulsivity/aggression

Although plasma-free or salivary testosterone is known to correlate better
with aggressiveness (Archer,
1991), our finding that plasma testosterone correlated positively
with life-time aggression and that mean testosterone levels were higher in
SHAPS impulsive aggressive psychopaths, compared with controls, supports early
reports that an early onset and a repetitive pattern of aggressiveness are
associated with elevated testosterone concentrations
(Virkkunen et al,
1994). A suggested mechanism for this link has been a reduction in
CORT's usual inhibition of luteinising hormone (LH) secretion due to low
plasma CORT resulting in greater stimulation of testosterone secretion by LH
(Mason et al, 1988).
We found a tendency towards higher testosterone and lower post-cannulation
CORT concentrations, but baseline CORT values did not differ between groups
and there was no inverse correlation between hormones, giving no direct
support to this theory. Differences in the measures of testosterone employed
in each study may account for the discrepancies.

Clinical Implications and Limitations

CLINICAL IMPLICATIONS

This study of aggressive offenders highlights the heterogeneity of
diagnosis of personality disorders within this population.

Serotonin (5-HT) function may particularly relate to the dimension of
behaviour control (inhibition-impulsivity) and suggest that serotonergic
agents may have a therapeutic role for some offenders with personality
disorders.

In offenders with personality disorders who have high impulsivity but low
anxiety levels, testosterone may also play a role in aggression control.

LIMITATIONS

The study sample may not be representative of offenders with aggressive
personality disorders in other non-hospital settings.

The biological measures used only provide an indirect measure of brain
function and hormonal influences.

The correlations between impulsivity, aggression and 5-HT function are
relatively weak and emphasise the need to investigate its relationship to
other important determinants of impulsive aggressive behaviour, such as
cognitive function.

Acknowledgments

We thank the staff and patients at Ashworth and Broadmoor hospitals for
their cooperation with this project, and Professors P. Taylor and R. Blackburn
for their support and assistance. We also thank Dr M. Franklin and staff at
the Psychopharmacology Unit, Littlemore Hospital, Oxford.